The first preliminary step to perform DEN is the localization of the most appropriate site to practice the cystoenterostomy (usually posterior gastric or median duodenal wall) [57]. This should always be conducted under EUS assistance, since it allows one to evaluate the extent of the collection, the amount of solid vs. liquid material, thickness of the wall, and the presence of interposed structures and blood vessels (using the Doppler flow guidance) [13,41,58]. In addition, if needed, it allows one to perform FNA with subsequent culture or GRAM stain, and to inject contrast to visualize the cavity under fluoroscopy [13,41,59]. The next step is different, depending on the kind of stent used:

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DPPS: with a needle assisted procedure, a guidewire is advanced under fluoroscopic guidance and dilation of the tract is performed with an ≥8 mm pneumatic balloon [29,30]. Two or more DPPSs of 7–10 F are positioned, in order to keep the stoma open for maturation and drain the content of the collection. Furthermore, using multiple DPPSs reduces the probability of stent occlusion and migration [30,31]. Subsequent dilations with balloons of increasing diameter (15–20 mm) are performed to obtain a cystoenterostomy of caliber big enough to advance the endoscope inside the cavity and perform the DEN. If there is a need to keep the cystoenterostomy open, multiple DPPSs are placed [23,30].

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LAMS: with a needle assisted procedure, a guidewire is advanced under fluoroscopic guidance and a dilation of the tract is performed with a 4–10 mm pneumatic balloon to facilitate the advancement of the LAMS delivery catheter over the wire. The distal flange is deployed under EUS guidance, traction is then applied to appose the distal flange against the cyst wall and bring it in firm apposition against the stomach/duodenal wall. The proximal flange was then deployed under endoscopic guidance [42] or with the intra-channel release technique [60].

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EC-LAMS: the deployment catheter is positioned on the selected point on the gastric/duodenal wall. The activation of the electro-cautery tip allows direct passage of the catheter into the collection under EUS guidance. The distal flange of the LAMS is deployed, and the next steps are the same as the LAMS (Figure 3) [50].

Figure 3. EUS image of the distal flange of an EC-LAMS deployed into a WOPN (left) and endoscopic view of the proximal flange after positioning the EC-LAMS (right).

Since the use of air instead of CO₂ for insufflation is a well-known cause of gas embolism during DEN, current international guidelines advice to avoid air insufflation when performing DEN [13,29,61]. In fact, after its introduction in DEN practice, no gas embolism events have been reported [13].

After performing DEN, a nasocystic catheter can be placed in parallel or through the stents to cautiously flush the collection with saline or hydrogen peroxide, avoiding forced injection of high fluid volumes, which may cause rupture of the cavity wall with fatal consequences [13,30,62,63].

After entering the collection, the fluids and little necrotic debris are sucked through the endoscope working channel. The bigger necrotic debris and those adherent to the wall are grabbed with various devices conceived for other purposes, like polypectomy snares (Figure 4), Dormia basket, Roth basket, other stone removal baskets and forceps of various shape (grasping, tripod, rat-tooth, pelican), and released into the stomach/duodenum [13,23,24,25,37,41,64]. In 2018 Van Der Wiel et al. reported the first two cases of WOPN treated with a novel device, the EndoRotor Powered Endoscopic Debridement (PED) System^® (Interscope Medical, Inc., Worcester, MA, USA) [65].

The EndoRotor^® is a through-the scope tool designed for use in the gastrointestinal tract for tissue dissection and resection, later modified to perform safely and efficaciously DEN. The instrument passes through a working channel of at least 3.2 mm and has a fixed outer cannula with a hollow inner cannula that rotates at either 1000 or 1700 revolutions per minute, as set up in the electronic control console, cutting 2–4 mm of tissue per second [65,66,67]. The inner cannula has an opening through which a 50–550 mmHg negative pressure allows one to collect the cut tissue into a trap or into a standard vacuum container; both the rotating and the suction function are controlled by the operator with two separate foot pedals [66,67,68].

After two small series by Van Der Wiel et al. [67] and Larghi et al. [68], reporting a successful use of the EndoRotor^® to perform DEN, Stassen et al. conducted the first multicenter prospective trial involving 30 patients with symptomatic WOPN requiring DEN, whose results were recently published on the Gastrointestinal Endoscopy Journal [69]. They reported a median number of 1.5 EndoRotor^®-assisted DENs required to achieve an average reduction of 85% in collection volume and 91% of necrotic debris. Three DEN-related AEs occurred (10% of patients), but none of them was classified as EndoRotor^®-related (two cases of stent-related bleeding, and one case of pneumoperitoneum due to the endoscope being torqued within the LAMS), with a mortality rate of 3%.

In each series authors expressed a positive opinion, especially about the short learning curve required to easily manipulate the tool, the possibility to constantly visualize the operating area with a low estimated risk of causing complications, and the fact that no repeated retrieval and insertion of the endoscope are needed to perform the necrosectomy [65,67,68].

These data suggest that the EndoRotor^® may be an effective and safe dedicated device to perform DEN, but further studies are required to confront classical and EndoRotor^®-assisted DEN.

Hydrogen peroxide (H₂O₂) is a colorless liquid which rapidly dissociates into oxygen and H₂O when in contact with organic tissues, producing a soft foam that helps removing materials attached to the tissue, including necrotic debris [70,71]. Furthermore, it seems help wounds healing by stimulating granulation and fibrosis [72]. In order to use its healing and chemical debridement properties, it has often been used as aid in DEN, despite lack of properly designed clinical trials to assess its efficacy, AEs, and technical aspects in such field [62].

For this reasons, current international guidelines suggest restraint regarding H₂O₂-assisted DEN [13,14]. Many series and comparative trials, published both prior to and after the publication of the guidelines, reported a high technical and clinical success of H₂O₂-assisted DEN, a reduced number and duration of DEN sessions, with sometimes no need at all for mechanical debridement, and an AEs profile and rate similar to non-H₂O₂-assisted DEN [70,72,73,74].

Such results were confirmed by a recent systematic review and meta-analysis by Garg et al. conducted on 15 studies involving a total of 454 patients who underwent H₂O₂-assisted DEN (median concentration 3%, range 0.1–3% with dilution and volume 1:1–1:10 and 20 mL to 1 L respectively) [71]. Their analysis reported a high technical and clinical success rate (97.3% and 89.8% respectively), with an AEs rate of 17.9% (bleeding, stent migration, and perforation), comparable to DEN performed without H₂O₂.

Several cases of gas embolism have been reported after H₂O₂ use in neurosurgery, orthopedic surgery, fistula irrigation and wound debridement [75,76,77,78,79,80]. This potentially lethal AE may be due to the rapid and high amount of free oxygen released after the contact with organic tissue (the breakdown of 20 mL of 3% H₂O₂ solution releases 200 mL of gaseous oxygen) [81]. To the best of our knowledge no case of such AE has been reported in the published H₂O₂-assisted DEN series. Some authors suggest that H₂O₂-induced gas embolism may be favored by its use into closed and semi-closed cavities, where oxygen release may cause an increase of the cavity pressure, facilitating gas passage into blood vessels [72,82]. Low flow saline irrigation may be a safer alternative practice to help performing DEN.

It is worth mentioning that in the literature there are a few reports of the successful use of an endoscopic vacuum-assisted therapy (EVAT) and the Endo-SPONGE (B. Braun, Melsungen, Germany) for facilitating infected WOPN healing after drainage and DEN [83,84,85,86,87]. The combined action of the Endo-SPONGE (which absorbs inflammatory fluids and induces tissue granulation), together with the negative pressure (which drains inflammatory fluids, increases vascularization and cell proliferation), should lead to a faster and easier resolution of the WOPN [86,87,88]. On the other hand, this procedure is not abhorrent from risks, as highlighted by Wallstabe et al. [84]. Performing EVAT in an area rich of important vascular structures such as the region of the celiac trunk and portal venous system carries, in theory, a higher risk of bleeding then performing the therapy in other body regions [89]. As outlined in the current guidelines, the amount of series of EVAT applied to WOPN is still too small to make this technique a standard of care for PNCs [13]. Furthermore, no randomized controlled trials have been performed yet and the potential AEs profile has not yet been established.

Timing of intervention in PNCs is still a hot topic among the scientific community. Postponing any invasive intervention until the PNC has walled-off is a surgery practice heritage, which has its roots in the increased mortality and complication rate after early open necrosectomy [18,89,90,91]. Current international guidelines advise to delay any invasive intervention until at least 4 weeks after the AP onset [2]. This seems a wise approach for those patients stable enough to wait for the collection to be walled-off, but emerging data are showing that early intervention is possible and advisable for patients with clinical deterioration despite maximum support [13,14,92].

A recent survey by van Grinsven et al. reported a lack of consensus among experts regarding timing and usefulness of early PNC intervention (both drainage and necrosectomy), showing that early intervention is already incorporated into clinical practice [93]. Van Grinsven et al. conducted a randomized controlled trial (POINTER trial) with the aim of better understanding whether immediate step-up approach (endoscopic or surgical) in patients with INP is superior to postponed step-up approach with regard to clinical outcome and cost-effectiveness [19]. Results were presented at the 2020 UEG week, showing no difference between the two strategies in mortality, new onset organ failure, major complications and hospital stay. Trikudanathan et al. conducted a study on 193 patients with ANP treated with endoscopic step-up approach and/or percutaneous catheter drainage when needed [92]. Interventions were categorized as early if timing of intervention was <4 weeks (76 patients), and standard if ≥4 weeks from onset of AP. They reported an increased in mortality rate (14% vs. 4%), need for rescue open necrosectomy, hospital and ICU stay in the “early intervention” group, with similar improvement in organ failure and similar complication rate. Albers et al. treated 49 patients with confirmed or suspected IPN with STGT or MTGT with LAMS (15 mm diameter × 10 mm length or 16 mm diameter × 20 mm length) after a median of seven days after the first proof of necrosis, when most of the necrotic collections were not expected to be encapsulated [12]. DEN was always performed during the same procedure, except for patients with sepsis, where DEN was performed post-recovery. They reported a 100% technical success, an 87.8% clinical success, and an 8.2% mortality rate, in line with previous studies and meta-analysis (5.7–14.5%) [24,29,32,57].